BACKGROUND:The pathogenesis of diabetic peripheral neuropathy has not yet been clarified,and TAM(Tyro3,Axl,and MerTK)receptor tyrosine kinases can control apoptotic cells and suppress inflammatory responses in the central nervous system. OBJECTIVE:To investigate the difference of Mer receptor tyrosine kinase(MerTK)levels in plasma and sciatic nerve tissue of Sprague-Dawley rats with type 2 diabetes and diabetic peripheral neuropathy,and to study the correlation between MerTK and diabetic peripheral neuropathy. METHODS:Forty male Sprague-Dawley were randomly divided into control group with 15 rats,type 2 diabetes group with 10 rats,and diabetic peripheral neuropathy group with 15 rats.The control group was fed with ordinary diet,while the experimental groups were fed with high-fat and high-sugar diet.After 6 weeks,intraperitoneal injection of streptozotocin at the minimum dose of 35 mg/kg was administered in the two experimental groups.After 14 days,tail vein blood was collected to detect blood glucose.If blood glucose≥16.7 mmol/L,the model of type 2 diabetes was successfully established.Rats in the diabetic peripheral neuropathy group continued to be fed with a high-sugar and high-fat diet for 8 weeks.The sciatic nerve conduction velocity of rats was detected through live isolation under anesthesia.Blood samples were collected from the abdominal aorta,and the sciatic nerve tissue was collected.Histological changes of nerve fibers in each group were observed under a light microscope to confirm the success of diabetic peripheral neuropathy modeling.ELISA was used to detect peripheral blood glucose,blood lipids and serum MerTK levels in rats;hematoxylin-eosin staining was used to observe the histological changes in the sciatic nerve;immunofluorescence,immunohistochemistry and western blot were used to detect the expression of MerTK in the sciatic nerve tissue. RESULTS AND CONCLUSION:The Sprague-Dawley rat models of type 2 diabetes and type 2 diabetes peripheral neuropathy were successfully constructed,and the modeling rate of diabetic peripheral neuropathy was 80%.Compared with the control group,the blood glucose levels of rats in the type 2 diabetes and diabetic peripheral neuropathy groups were significantly higher(P<0.000 1),while the blood glucose level in the diabetic peripheral neuropathy group was higher than that in the type 2 diabetes group;and the sciatic nerve conduction velocity was significantly decreased(P<0.05),which was lower in the diabetic peripheral neuropathy group than the type 2 diabetes group.Histological examination:Compared with the control group,the sciatic nerve nuclei were reduced in the type 2 diabetes group,with some vacuolar degeneration and phagocytosis;in the diabetic peripheral neuropathy group,the cell body was swollen,the nuclear spacing was increased,vacuolar degeneration was observed,and the myelin sheath was partitioned and unsmooth,and lattice-like axons appeared.Serum MerTK levels were significantly higher in the diabetic peripheral neuropathy group than the control group.Expression of MerTK in the sciatic nerve tissue was significantly upregulated in the diabetic peripheral neuropathy group compared with the control group(P<0.05).To conclude,elevated levels of MerTK in plasma and sciatic nerve tissue of rats with diabetic peripheral neuropathy are presumably related to its anti-inflammatory and immunomodulatory effects.

OBJECTIVE To explore the effect of volatile oil of Ligusticum chuanxiong on the transdermal properties and cytotoxicity of triptolide in vitro. METHODS The chemical constituents of the volatile oil of L. chuanxiong were analyzed by gas chromatography-mass spectrometry. The lower abdominal skin of KM mice was separated and divided into triptolide group， triptolide in compatibility with volatile oil of L. chuanxiong groups at 1∶10， 1∶50， 1∶100 （hereinafter referred to as “compatibility 1∶10”“compatibility 1∶50”“compatibility 1∶100” groups）. After the skin of mice in each group was fully exposed to 0.2 g of the corresponding cream for 24 h， the cumulative transdermal dose （Qn） of triptolide in the receiving solution of each group was determined by high-performance liquid chromatography， and the transdermal absorption rate （Jss） was calculated. Human immortalized keratinocytes （HaCat） were used as a model， the CCK-8 method was used to detect the cell survival rate of different concentrations of the volatile oil of L. chuanxiong and triptolide before and after compatibility. RESULTS A total of 62 chemical constituents of the volatile oil of L. chuanxiong were identified， including Z-ligustilide， senkyunolide， and β-selinene. The Qn （P＜ 0.01） and Jss of triptolide increased within 24 h in the compatibility 1∶10 and 1∶50 groups， while the Qn （P＜0.05） and Jss decreased in the compatibility 1∶100 group as compared with the triptolide group. Compared with the triptolide group， the cell survival rate of HaCat was significantly increased in the compatibility 1∶10 and 1∶50 groups when the triptolide concentrations were 36， 72 and 144 ng/mL （P＜0.05 or P＜0.01）； while the cell survival rate of HaCat was decreased in the compatibility 1∶100 group， but the difference was not statistically significant （P＞0.05）. CONCLUSIONS When the compatibility ratio of triptolide and volatile oil of L. chuanxiong was 1∶10 or 1∶50， it can promote the transdermal absorption of triptolide and reduce the cytotoxicity of triptolide to HaCat.

Diabetic ulcer (DU), one of the common and serious complications in patients with diabetes mellitus, often leads to infection, necrosis and amputation, and has a long and costly treatment period. Because of DU's unclear healing mechanism and the difficulty of delayed healing, its treatment and management have been a major challenge in clinical medicine. In recent years, the potential role of mitochondrial autophagy in DU has become a research hotspot with the in-depth study of mitochondrial autophagy mechanism. Previous studies have shown that mitochondrial autophagy is an important intracellular self-repair mechanism that plays a crucial role in maintaining cellular health and functional stability. During the development of DU, mitochondrial autophagy plays multiple roles in attenuating oxidative stress and inflammatory responses, maintaining mitochondrial functional homeostasis, influencing cell proliferation and repair capacity during DU healing, promoting DU healing, and enhancing antimicrobial capacity. In this paper, we illustrate the multiple roles played by mitochondrial autophagy in DU prevention and treatment, as well as the potential applications of mitochondrial autophagy in DU therapy. It is expected to provide a basis for the clinical application of mitochondrial autophagy in DU treatment, and provide more effective strategies and solutions for the treatment of DU.

Diabetic ulcer (DU), one of the common and serious complications in patients with diabetes mellitus, often leads to infection, necrosis and amputation, and has a long and costly treatment period. Because of DU's unclear healing mechanism and the difficulty of delayed healing, its treatment and management have been a major challenge in clinical medicine. In recent years, the potential role of mitochondrial autophagy in DU has become a research hotspot with the in-depth study of mitochondrial autophagy mechanism. Previous studies have shown that mitochondrial autophagy is an important intracellular self-repair mechanism that plays a crucial role in maintaining cellular health and functional stability. During the development of DU, mitochondrial autophagy plays multiple roles in attenuating oxidative stress and inflammatory responses, maintaining mitochondrial functional homeostasis, influencing cell proliferation and repair capacity during DU healing, promoting DU healing, and enhancing antimicrobial capacity. In this paper, we illustrate the multiple roles played by mitochondrial autophagy in DU prevention and treatment, as well as the potential applications of mitochondrial autophagy in DU therapy. It is expected to provide a basis for the clinical application of mitochondrial autophagy in DU treatment, and provide more effective strategies and solutions for the treatment of DU.

Objective: To investigate the level and influencing factors of health literacy among the elderly in Gannan Tibetan Autonomous Prefecture, Gansu Province, so as to provide the evidence for developing the strategy to improve health literacy among the elderly. Methods: A total of 3 125 residents at ages of 60 years and older were recruited from Gannan Tibetan Autonomous Prefecture with a multistage random cluster sampling method from June to September, 2021. The level of health literacy was investigate among the elderly using the Questionnaire on the Health Literacy among Chinese Residents, and factors affecting the health literacy were identified using a multivariable logistic regression model. Results: A total of 3 125 questionnaires were allocated and 3 022 valid questionnaires were recovered, with an effective recovery rate of 96.70%. The respondents included 1 562 men (51.69%) and 1 460 women (48.31%), and had a mean age of (67.37±5.78) years. The participants included 1 234 individuals with an ethnic minority (40.83%). The overall prevalence of health literacy was 5.99% among participants, and the prevalence rates of basic healthy knowledge and attitudes, healthy lifestyles and behaviors and basic health-related skills were 13.57%, 8.97% and 7.67%, respectively. Multivariable logistic regression analysis identified Han Ethnicity (OR=2.266, 95%CI: 1.497-3.431), educational level (illiteracy/semi-illiteracy, OR=0.097, 95%CI: 0.038-0.246; primary school, OR=0.125, 95%CI: 0.051-0.303; junior high school, OR=0.276, 95%CI: 0.113-0.672; high school/vocational high school/technical secondary school, OR=0.307, 95%CI: 0.125-0.757), enterprise workers (OR=1.791, 95%CI: 1.089-2.947) and annual household income of less than 10 000 RMB (OR=0.526, 95%CI: 0.294-0.940) as factors affecting health literacy among the elderly in Gannan Tibetan Autonomous Prefecture. Conclusions The level of health literacy is low among the elderly in Gannan Tibetan Autonomous Prefecture, and ethnicity, educational level, occupation and annual household income are main factors affecting the level of health literacy among the elderly in Gannan Tibetan Autonomous Prefecture.

OBJECTIVES: Long-term hepatitis B virus (HBV) infection can cause recurrent inflammation in the liver, and then develop into liver fibrosis, cirrhosis, and liver cancer. The hepatic pathological change is one of the important criteria for guiding antiviral therapy in patients with chronic hepatitis B (CHB). Due to the limitations of liver biopsy, it is necessary to find valuable non-invasive indicators to evaluate the hepatic pathological changes in CHB patients and guide the antiviral therapy. This study aims to analyze the clinical characteristics of different pathological changes in CHB patients, and to explore the factors influnencing the degree of liver inflammation and fibrosis in CHB patients with normal alanine aminotransferase (ALT). METHODS: This retrospective study was conducted on 310 CHB patients. Liver biopsy was performed in all these patients. The clinical data of the patients were collected. The liver biopsy pathological results were used as the gold standard to analyze the relationship between clinical indicators and liver pathological changes. Then CHB patients with normal ALT were screened, and the independent factors influencing the degree of liver inflammation and fibrosis were explored. RESULTS: Among the 310 patients with CHB, there were 249 (80.3%) patients with significant liver inflammation [liver inflammation grade (G) ≥2] and 119 (38.4%) patients with significant liver fibrosis [liver fibrosis stage (S) ≥2]. The results of univariate analysis of total samples showed that the ALT, γ-glutamyl transferase, alkaline phosphatase, and HBV DNA were related to the significant liver pathological changes. Among the 132 CHB patients with normal ALT, the patients with liver pathology G/S≥2, G≥2, and S≥2 were 80.3% (106/132), 68.2% (90/132), and 43.2% (57/132), respectively. The results showed that the independent influencing factor of significant liver inflammation was HBV DNA>2 000 U/mL (OR=3.592, 95% CI 1.534 to 8.409), and the independent influencing factors of significant liver fibrosis were elevated alkaline phosphatase level (OR=1.022, 95% CI 1.002 to 1.043), decreased platelet count (OR=0.990, 95% CI 0.982 to 0.998), and positive in hepatitis B e antigen (HBeAg) (OR=14.845, 95% CI 4.898 to 44.995). According to the multivariate analysis, a diagnostic model for significant liver fibrosis in CHB patients with normal ALT was established, and the area under the receiver operating characteristic curve was 0.844 (95% CI 0.779 to 0.910). CONCLUSIONS The liver pathological changes should be evaluated in combination with different clinical indicators. A considerable number of CHB patients with normal ALT still have significant liver pathological changes, which need to be identified and treated with antiviral therapy in time. Among them, HBV DNA>2 000 U/mL suggests the significant liver inflammation, and the diagnostic model for significant liver fibrosis based on alkaline phosphatase, platelet count, and HBeAg can help to evaluate the degree of liver fibrosis.
Humans ; Hepatitis B, Chronic/complications* ; Hepatitis B e Antigens/therapeutic use* ; Alkaline Phosphatase ; DNA, Viral ; Retrospective Studies ; Fibrosis ; Hepatitis B virus/genetics* ; Liver Cirrhosis/etiology* ; Inflammation/drug therapy* ; Antiviral Agents/therapeutic use* ; Alanine Transaminase

Objective:To study the effects of electron beam irradiation and 60Co irradiation on the composition changes of four alkaloids in Sophorae Flavescentis Radix, intermediate extracts of Sophorae Flavescentis Radix and Lixieling Tablets. Methods:Sophorae Flavescentis Radix, intermediate extracts of Sophorae Flavescentis Radix and Lixieling Tablets were irradiated at different doses of 0, 1.5, 3, 5, 7, 10, 20, 30, 40 kGy by electron beam irradiation and 60Co irradiation. The contents of oxymatrine, oxysophocarpine, matrine and sophocarpine were determined by HPLC, and the changes of the components before and after irradiation were compared. Results:Oxymatrine, oxysophocarpine, matrine and sophocarpine were among 0.046 9-0.937 4 μg, 0.020 5-0.410 4 μg, 0.098 9-1.977 9 μg, 0.048 7-0.973 1 μg, respectively. The linear relationship was good. The average recovery rates were 98.1%, 100.1%, 100.5%, 96.6%, respectively, and the RSDs were 1.69%, 2.03%, 3.14% and 1.10%, respectively. Electron beam irradiation and 60Co irradiation had no statistical significance on the changes of oxymatrine, oxysophocarpine, matrine and sophocarpine in Sophora flavescens, but had statistical significance in the contents of intermediate extracts of Sophorae Flavescentis Radix and Lixieling Tablets. Conclusion:The established method for the determination of matrine is accurate, reproducible, simple and practical, and can be used for the quality control of Lixieling Tablets. Irradiation has no significant effect on the content of Sophorae Flavescentis Radix, while high dose irradiation has significant effect on the intermediates and finished products of Sophorae Flavescentis Radix, which can provide a basis for quality control and sterilization irradiation of enterprises.

Objective To explore the regulatory effect of Mertk expression level on NF-κb pathway in rat Schwann cells and its possible mechanism.Methods Rat Schwann cells were cultured in vitro,and the expression of Mertk in Schwann cells exposed to high glucose was detected by Western blot.Co-immunoprecipitation was used to detect the interaction between endogenous Mertk and Ikbkb.Western blot was used to detect the expression levels of Ikbkb,P65 and tumor necrosis factor-α in Schwann cells after Mertk silencing.The protein expressions of Mertk,Ikbkb and P65 after silencing Mertk were detected by immunofluorescence.Results Mertk was expressed in Schwann cells,and the expression level increased with the increase of glucose concentration.Co-immunoprecipitation assay showed that Mertk interacted with Ikbkb in rat Schwann cells.Compared with the control group,the expression level of Mertk was significantly decreased(P<0.05),while Ikbkb,P65 and TNF-α were significantly increased(P<0.05)after knock down expression of Mertk in Schwann cells.Immunofluorescence experiments showed that the fluorescence of Mertk was decreased,and the fluorescence of Ikbkb and P65 was increased in the silenced Schwann cells.Conclusion After the expression of Mertk is decreased,it can mediate the regulation of NF-κb pathway in Schwann cells through interaction with Ikbkb,and up-regulate the expression of P65 and inflammatory factor TNF-α.

Objective:To analyze the efficacy of the new forest parenting programme (NFPP) for children and families with attention deficit hyperactivity disorder (ADHD) in China, and to explore the feasibility and effectiveness of the programme in China.Methods:Twenty-two children with ADHD diagnosed at the Child Psychology Development and Behavior Outpatient Clinic of the First Affiliated Hospital of Jinan University and their primary caregivers were included in the study from January 2022 to May 2023. The children with ADHD were divided into an experimental group ( n=11) and a control group ( n=11) according to the personal preference of the primary caregivers. The experimental group was provided with the NFPP intervention once a week for a period of 8 weeks. The Chinese version of Swanson Nolan and Pelham, version Ⅳ scale-parent form(SNAP-Ⅳ)and Weiss functional impairment rating scales-parent report(WFIRS-P))were used to assess the improvement of core symptoms and social function impairment in the two groups before and after the intervention. In the experimental group, the Chinese parenting sense of competence scale (C-PSOC) and the parenting styles and dimensions questionnaire (PSDQ) were used to evaluate the parenting efficiency and improvement of parenting styles of primary caregivers in ADHD families before and after NFPP intervention. A Semi-open interview was conducted with 11 primary caregivers of ADHD children in the experimental group at the end of the intervention regarding knowledge of ADHD disease diagnosis and treatment, parenting attitudes, and parenting behaviors. The data was statistically analyzed by SPSS 26.0 software.Statistical analysis of data was used by independent sample t-test, paired sample t-test, Mann Whitney U-test, and rank sum test. Results:(1) Compared with the post-intervention control group, the total score((4.01±1.05), (2.79±0.94), t=2.875, P<0.05) in the SNAP-Ⅳ, the scores of the oppositional defiance dimension((1.27±0.34), (0.70±0.33), t=4.043, P<0.05) in the SNAP-Ⅳ, the scores of the family in WFIRS-P ((0.92±0.47), (0.56±0.26), t=2.246, P<0.05), and the scores of life skills in WFIRS-P (1.1(0.9, 1.3), (0.6(0.5, 0.8), Z=-2.013, P<0.05)were significantly lower in the post-intervention experimental group ( P<0.05). After intervention, the scores of the 3 dimensions of attention deficit, impulsivity/hyperactivity, and oppositional defiance and the total score of the SNAP-Ⅳ in the experimental group were significantly lower than those before intervention (all P<0.05). (2) After intervention, the score of the parenting efficacy dimension in the C-PSOC in experimental group was significantly higher than pre-intervention ( P<0.05). After intervention, the scores of the PSDQ for authoritative parenting style in the self-assessment and other-assessment in the experimental group were significantly higher than pre-intervention (all P<0.05), and the scores of the authoritarian parenting style and the permissive parenting style were significantly lower than pre-intervention (all P<0.05). (3) The results of the semi-open interview suggested that, the primary caregivers of children with ADHD in the experimental group had a positive attitude toward the NFPP intervention and were able to participate in the entire 8-week intervention, and apply the learned parenting skills to daily life to continuously improve parenting efficiency. After the NFPP intervention, the primary caregivers of children with ADHD had a deeper understanding of the knowledge of ADHD diseases, behavioral characteristics of children with ADHD, and so on. In the intervention content, the modules such as time management, communication skills and behavioral prediction were easy to grasp and effective. Conclusion:The NFPP can significantly improve the core symptoms of Chinese children with ADHD, increase the parenting efficacy of their primary caregivers, and improve their parenting styles.

OBJECTIVE To establish the quality standard of Lixieling tablets. METHODS Thin layer chromatography was used to identify Bistortae Rhizoma, Andrographis Herba and Sophorae Flavescentis Radix in Lixieling tablets. The components of andrographolium and matrine were determined by HPLC. RESULTS The thin layer spots of Bistortae Rhizoma, Andrographis Herba and Sophorae Flavescentis Radix were clear, with good separation effect and repeatability. The linear relationship between andrographolide, neoandrographolide, 14-deoxygenated andrographolide, dehydrated andrographolide, sophorine, oxymatrine, sophorine and oxysophorine and their respective concentration ranges was good. The RSDs of instrument precision, repeatability, stability and recovery all met the requirements. CONCLUSION The method is simple and reproducible, and can be used for the quality control of Lixieling tablets.